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Endpoint:
biochemical or cellular interactions
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: data from iCSS CompTox Dashboard. Data Quality 100%. Data manually curated with highest confidence
Principles of method if other than guideline:
Using a high-throughput robotic screening system, TBEC was assessed for its potential to disrupt biological pathways (DNA binding, growth factor, nuclear receptor (non-steroidal and steroidal), cell cycle, cytochrome P450, hydrolase and cell morphology) that may result in toxicity.
Type of method:
in vitro
Specific details on test material used for the study:
DSSTOX GSID: 44921
Remarks:
0.0006 to 90µM
Details on study design:
See enclosed excel file
Details on results:
113 assays were performed. TBEC was inactive in all assays, therefore, there is no evidence that TBEC could interfere with the expression of the screened genes.

113 assays were performed, all results are displayed in the enclosed excel file.

TBEC was inactive in all assay (see attached figure).

 

Executive summary:

Using a high-throughput robotic screening system, TBEC was assessed for its potential to disrupt biological pathways (DNA binding, growth factor, nuclear receptor (non-steroidal and steroidal), cell cycle, cytochrome P450, hydrolase and cell morphology) that may result in toxicity. 113 assays were performed. TBEC was inactive in all assays, therefore, there is no evidence that TBEC could interfere with the expression of the screened genes.

Endpoint:
biochemical or cellular interactions
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Principles of method if other than guideline:
The PubChem BioAssay database was searched for chemogenomic, medicinal chemistry and functional genomics biological activities
Type of method:
in vivo
Specific details on test material used for the study:
PubChem CID: 61931
PubChem SID: 144211602




Details on results:
150 bioassays with 150 bioactivity outcomes were retrieved from the PubChem BioAssay data base. TBEC was reported as inactive in 137 biossays, inconclusive in 12 bioassays and active in 1 cytotoxicity bioassay. Nevertheless, according to the detailed results of this cytotoxicity assay, there was no demonstration of a toxicological activity.

The list of all the assays performed is displayed in the enclosed excel file.

Detailed data on the assay reported as positive are displayed below and in the attached figure.

Activity Value [µM]

Substance SID

BioAssay AID

BioAssay Name

48.9662

144211602

743209

qHTS assay for small molecule activators of the heat shock response signaling pathway - cell viability counter screen

Data for SID 144211602 in AID 743209

Phenotype-Replicate_1

Cytotoxic

Potency-Replicate_1 [uM]*

48.9662

Efficacy-Replicate_1 [%]

80.4056

Analysis Comment-Replicate_1

Activity_Score-Replicate_1

41

Curve_Description-Replicate_1

Partial curve; high efficacy

Fit_LogAC50-Replicate_1

-4.3101

Fit_HillSlope-Replicate_1

2.9023

Fit_R2-Replicate_1

0.9315

Fit_InfiniteActivity-Replicate_1 [%]

-79.6205

Fit_ZeroActivity-Replicate_1 [%]

0.7851

Fit_CurveClass-Replicate_1

-2.1

Excluded_Points-Replicate_1

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

Max_Response-Replicate_1 [%]

-62.9701

Activity at 0.00107 uM-Replicate_1 [%]

-3.289

Activity at 0.00238 uM-Replicate_1 [%]

-0.5705

Activity at 0.00531 uM-Replicate_1 [%]

1.9899

Activity at 0.012 uM-Replicate_1 [%]

-4.3088

Activity at 0.026 uM-Replicate_1 [%]

9.1788

Activity at 0.059 uM-Replicate_1 [%]

3.3052

Activity at 0.132 uM-Replicate_1 [%]

-6.3236

Activity at 0.275 uM-Replicate_1 [%]

-5.0525

Activity at 0.550 uM-Replicate_1 [%]

3.6889

Activity at 1.225 uM-Replicate_1 [%]

8.459

Activity at 2.701 uM-Replicate_1 [%]

0.678

Activity at 5.947 uM-Replicate_1 [%]

1.6567

Activity at 13.22 uM-Replicate_1 [%]

-4.8617

Activity at 29.14 uM-Replicate_1 [%]

-18.3784

Activity at 62.57 uM-Replicate_1 [%]

-62.9701

Compound QC-Replicate_1

QC'd by SIGMA

Phenotype-Replicate_2

Inactive

Max_Response-Replicate_2 [%]

15.201

Activity at 0.00107 uM-Replicate_2 [%]

26.1066

Activity at 0.00238 uM-Replicate_2 [%]

1.123

Activity at 0.00531 uM-Replicate_2 [%]

-0.4973

Activity at 0.012 uM-Replicate_2 [%]

18.7334

Activity at 0.026 uM-Replicate_2 [%]

12.6056

Activity at 0.059 uM-Replicate_2 [%]

12.5507

Activity at 0.132 uM-Replicate_2 [%]

0.7704

Activity at 0.275 uM-Replicate_2 [%]

2.2138

Activity at 0.550 uM-Replicate_2 [%]

19.2095

Activity at 1.225 uM-Replicate_2 [%]

2.6449

Activity at 2.701 uM-Replicate_2 [%]

8.3207

Activity at 5.947 uM-Replicate_2 [%]

24.1029

Activity at 13.22 uM-Replicate_2 [%]

1.1825

Activity at 29.14 uM-Replicate_2 [%]

10.9219

Activity at 62.57 uM-Replicate_2 [%]

15.201

Phenotype-Replicate_3

Inactive

Max_Response-Replicate_3 [%]

-16.9007

Activity at 0.00107 uM-Replicate_3 [%]

-20.298

Activity at 0.00238 uM-Replicate_3 [%]

-23.115

Activity at 0.00531 uM-Replicate_3 [%]

0

Activity at 0.012 uM-Replicate_3 [%]

-30.2343

Activity at 0.026 uM-Replicate_3 [%]

0

Activity at 0.059 uM-Replicate_3 [%]

-7.8363

Activity at 0.132 uM-Replicate_3 [%]

-4.6272

Activity at 0.275 uM-Replicate_3 [%]

-11.0875

Activity at 0.550 uM-Replicate_3 [%]

-13.2885

Activity at 1.225 uM-Replicate_3 [%]

-9.6367

Activity at 2.701 uM-Replicate_3 [%]

1.2267

Activity at 5.947 uM-Replicate_3 [%]

-20.8329

Activity at 13.22 uM-Replicate_3 [%]

-8.8938

Activity at 29.14 uM-Replicate_3 [%]

-1.869

Activity at 62.57 uM-Replicate_3 [%]

-16.9007

 

Executive summary:

The PubChem BioAssay database was searched for chemogenomic, medicinal chemistry and functional genomics biological activities. 150 bioassays with 150 bioactivity outcomes were retrieved. TBEC was reported as inactive in 137 biossays, inconclusive in 12 bioassays and active in 1 cytotoxicity bioassay. Nevertheless, according to the detailed results of this cytotoxicity assay, there was no demonstration of a toxicological activity. Therefore, TBEC is devoied of activity in cell viability assays, and of agonist and/or antagonist activities on the peroxisome proliferator-activated receptor alpha (PPARa), delta (PPARd) and gamma (PPARg), antioxidant response element (ARE), androgen receptor (AR), estrogen receptor alpha (ER-alpha), thyroid receptor (TR) and glucocorticoid receptor (GR), p53, vitamin D receptor, retinoic acid receptor (RAR), farnesoid-X-receptor (FXR), hypoxia (HIF-1), NFkB, RXR, retinoid-related orphan receptor gamma (ROR-gamma) and aryl hydrocarbon receptor (AhR) signaling pathways.

Description of key information

Using a high-throughput robotic screening system (US EPA, 2017), TBEC was assessed for its potential to disrupt biological pathways (DNA binding, growth factor, nuclear receptor (non-steroidal and steroidal), cell cycle, cytochrome P450, hydrolase and cell morphology) that may result in toxicity. 113 assays were performed. TBEC was inactive in all assays, therefore, there is no evidence that TBEC could interfere with the expression of the screened genes.

The PubChem BioAssay database was searched for chemogenomic, medicinal chemistry and functional genomics biological activities (NCBI, 2017). 150 bioassays with 150 bioactivity outcomes were retrieved. TBEC was reported as inactive in 137 biossays, inconclusive in 12 bioassays and active in 1 cytotoxicity bioassay. Nevertheless, according to the detailed results of this cytotoxicity assay, there was no demonstration of a toxicological activity. Therefore, TBEC is devoied of activity in cell viability assays, and of agonist and/or antagonist activities on the peroxisome proliferator-activated receptor alpha (PPARa), delta (PPARd) and gamma (PPARg), antioxidant response element (ARE), androgen receptor (AR), estrogen receptor alpha (ER-alpha), thyroid receptor (TR) and glucocorticoid receptor (GR), p53, vitamin D receptor, retinoic acid receptor (RAR), farnesoid-X-receptor (FXR), hypoxia (HIF-1), NFkB, RXR, retinoid-related orphan receptor gamma (ROR-gamma) and aryl hydrocarbon receptor (AhR) signaling pathways.

Additional information